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Investigation of Solubility Enhancement Approaches of Ticagrelor
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ABSTRACT

                   Ticagrelor is an orally administered antiplatelet medicine, direct-acting P2Y12-receptor antagonist. Ticagrelor binds reversibly and noncompetitively to the P2Y12 receptor at a site distinct from that of the endogenous agonist adenosine diphosphate (ADP). Inhibition of platelet aggregation stimulated by ADP is a commonly used pharmacodynamic parameter for P2Y12-receptor antagonists.

                  Ticagrelor is a crystalline powder with an aqueous solubility of approximately 10?g/mL at room temperature. Ticagrelor exhibits no pKa value within the physiological range. Ticagrelor does not exhibit pH-dependent solubility and is defined as ‘low solubility low permeability’ under the Biopharmaceutics Classification System (Class IV). The mean absolute bioavailability of ticagrelor in healthy volunteers is 36 %

                   Nanoparticles preparation and complexation is one of the recently used approaches to enhance the solubility of drugs. The aim of the present work was to improve the solubility and dissolution of ticagrelor by preparing nanoparticles and cyclodextrin inclusion complex of ticagrelor and then incorporated in to tablet dosage form. Fifteen formulas of nanoparticles were prepared by antisolvent precipitation method (solvent displacement method) utilizing one of the three polymers (PVP, Poloxamer, and HPMC) at three different drugs: polymer and solvent: anti-solvent ratios and nine formulas of cyclodextrin inclusion complex with HP?CD  by three preparation methods, physical trituration, kneading and solvent evaporation, which increase the solubility and dissolution rate of ticagrelor via formation of inclusion complex with HP?CD.

              The prepared formulas were characterized regarding the saturated solubility, polydispersity index, particle size by nano laser particle size analyzer, % yield, entrapment efficiency, and flowability, FTIR, DSC, and SEM. The selected formulas were prepared as tablets.

             The prepared tablets were evaluated for drug content, weight variation, hardness, and friability. In vitro dissolution data of the prepared tablets were analyzed using similarity factor (f2) and dissolution efficiency (DE).  

           Among all the prepared nanoparticles formulas, formula (F12) which contain HPMC as a polymer at polymer: drug ratio of (1:1) and solvent: antisolvent ratio of (1:1) was considered as the optimum formula which shows good evaluation parameters in addition to the increment in the solubility to about 9 times than that of the pure drug. The nanoparticle of the selected formula (F12) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 88 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).  Moreover, the analysis by DSC and SEM of the nanoparticles of the selected formula (F12) indicate a reduction in the crystallinity and amorphization of the drug. It can be concluded that the selected formula is a promising formula for the preparation of ticagrelor nanoparticles the incorporation in a tablet dosage form.

          Regarding ticagrelor inclusion complex with HP?CD Solvent evaporation method was the most effective method regarding ticagrelor solubilization and optimum formula of inclusion complex (F23) show increment in saturated solubility about ten times that of pure drug.

          The ticagrelor inclusion complex of the selected formula (F23) incorporated tablets showed an acceptable tablet properties in addition to a considerable increase in the dissolution efficiency to (DE=92 % and 90 % in PH 1.2 and PH 6.8 respectively) in comparison to that of the marketed tablet (DE=89% and 85% in PH 1.2 and PH 6.8 respectively).  

 

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Publication Date
Fri Jan 01 2021
Journal Name
Journal Of Engineering
A Computational Fluid Dynamics Investigation of using Large-Scale Geometric Roughness Elements in Open Channels
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The hydraulic behavior of the flow can be changed by using large-scale geometric roughness elements in open channels. This change can help in controlling erosions and sedimentations along the mainstream of the channel. Roughness elements can be large stone or concrete blocks placed at the channel's bed to impose more resistance in the bed. The geometry of the roughness elements, numbers used, and configuration are parameters that can affect the flow's hydraulic characteristics. In this paper, velocity distribution along the flume was theoretically investigated using a series of tests of T-shape roughness elements, fixed height, arranged in three different configurations, differ in the number of lines of roughness element

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Publication Date
Thu Jun 10 2010
Journal Name
Iraqi Journal Of Laser
Experimental Investigation of a Laser Wireless Video Communication System Using Intensity Modulated /Direct Detection Technique
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In this work Laser wireless video communication system using intensity modualtion direct
detection IM/DD over a 1 km range between transmitter and receiver is experimentally investigated and
demonstrated. Beam expander and beam collimeter were implemented to collimete laser beam at the
transmitter and focus this beam at the receiver respectively. The results show that IM/DD communication
sysatem using laser diode is quite attractive for transmitting video signal. In this work signal to noise
ratio (S/N) higher than 20 dB is achieved in this work.

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Publication Date
Wed Oct 09 2024
Journal Name
Engineering, Technology & Applied Science Research
Experimental Investigation of Composite Circular Encased GFRP I-Section Concrete Columns under Different Load Conditions
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Pultruded materials made of Fiber-Reinforced Polymer (FRP) come in a broad range of shapes, such as bars, I-sections, C-sections, etc. FRP materials are starting to compete with steel as structural materials owing to their great resistance, low self-weight, and cheap maintenance costs, especially in corrosive conditions. This study aims to evaluate the effectiveness of a novel concrete Composite Column (CC) using Encased I-Section (EIS) as a reinforcement in contrast to traditional steel bars by using Glass Fiber-Reinforced Polymer (GFRP) as I-section (CC-EIS) to evaluate the effectiveness of the hybrid columns which have been built by combining GFRP profiles with concrete columns. To achieve the aims of this study, nine circular co

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Publication Date
Mon Mar 29 2021
Journal Name
Eureka: Physics And Engineering
INVESTIGATION ON THE AIR-GAS CHARACTERISTICS OF AIR-HYDROGEN MIXER DESIGNED FOR DUAL FUEL – ENGINES
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High smoke emissions, nitrogen oxide and particulate matter typically produced by diesel engines. Diminishing the exhausted emissions without doing any significant changes in their mechanical configuration is a challenging subject. Thus, adding hydrogen to the traditional fuel would be the best practical choice to ameliorate diesel engines performance and reduce emissions. The air hydrogen mixer is an essential part of converting the diesel engine to work under dual fuel mode (hydrogen-diesel) without any engine modification. In this study, the Air-hydrogen mixer is developed to get a homogenous mixture for hydrogen with air and a stoichiometric air-fuel ratio according to the speed of the engine. The mixer depends on the balance between th

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Publication Date
Thu Sep 01 2022
Journal Name
Journal Of Engineering
Experimental Investigation of Crack Initiation and Growth in Concrete Slabs Placed Directly on Clayey Soil
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The main objective of this study is to examine the impact of moisture concrete of clayey soil on the concrete slabs placed directly over it. This experimental study presents the mechanical properties of the concrete slab when placed on different clayey soil moisture content ranging from 0% to the optimum moisture content of 35%. The tests were performed on soil concrete specimens of 25*30*50 mm exposed to sprayed water curing conditions for 28 days. Tests of compressive strength, ultrasonic pulse velocity, crack depth and crack width were investigated through this paper. An ejection relationship between compressive strength of concrete and water content in the soil was observed, with a 26% increase with water increasing from 0% to 35%. T

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Publication Date
Thu May 09 2024
Journal Name
Polymer Bulletin
Synthesis, characterization and investigation of liquid crystalline properties for some cross-link polymers containing melamine
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Publication Date
Sat Jun 19 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Investigation of Some Phytochemical Compounds Found in Anchusa strigosa L. Grown Naturally in Iraq
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Anchusa strigosa L.: Hardy annual biennial or perennial herb, with hairs especially on the leaves., flowers generally regular. Commonly named (Lisan Althour) in Iraq, from Boraginaceae family. The plant contains phenolic acids, flavonoids, alkaloids, sterols, and terpenoids. The Whole plant part defatted with n-hexane for 24 hours. The defatted plant material extracted using absolute methanol by Soxhlet apparatus for 24 hours, the extract fractionated by solvents of different polarity: petroleum ether- chloroform - ethylacetate- and n-butanol respectively. The n-butanol fraction hydrolyzed with 10% HCl for 5 hours by reflex to break down the glycosidic linkage. Rosmarinic acid, caffeic acid, genistein, and silybin were isolated

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Publication Date
Sun Apr 08 2018
Journal Name
Al-khwarizmi Engineering Journal
Experimental Investigation of the Effect of Curvature Ratio on Heat Transfer in Double Pipe Helical Heat Exchanger
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Different parameters of double pipe helical coil were investigation experimentally. Four coils were used; three with a curvature ratio (0.037, 0.031, and 0.028) and 11mm diameter of the inner tube while the fourth with 0.033 curvature ratio and 13 mm diameter of the inner tube. The hot water flow in the inner tube whereas the cold water flows in the annulus. The inlet temperatures of hot and cold water are 50 0C and 18 0C respectively. The inner mass flow rate ranges from 0.0167 to 0.0583 kg/s. The results show the Nusselt number increase with increase curvature ratio. The Nusselt number of the coil with 0.037 curvature ratio increases by approximately 12.3 % as compare with 0.028 curvature ratio. The results also r

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Publication Date
Sun Jun 07 2009
Journal Name
Baghdad Science Journal
Investigation of the Optical Properties of the Achromatic Quadrupole Lens by Using the Rectangular Potential Distribution Model
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An optimization calculation is made to find the optimum properties of combined quadrupole lens which consists of electrostatic and magnetic lens. Both chromatic and spherical aberration coefficients are reduced to minimum values and the achromatic aberration is found for many cases. These calculations are achieved with the aid of transfer matrices method and using rectangular model of field distribution, where the path of charged-particles beam traversing the field has been determined by solving the trajectory equation of motion and then the optical properties for lens have been computed with the aid of the beam trajectory along the lens axis. The computations have been concentrated on determining the chromatic and spher

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Publication Date
Thu Dec 01 2016
Journal Name
Journal Of Engineering
Analytical and Experimental Investigation for the Effect of Air Injection Angle on the Performance of Airlift Pump
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The effect of air injection angle on the performance of airlift pump used for water pumping has been studied analytically and experimentally. An airlift pump of dimensions 42mm diameter and 2200 mm length with conventional and modified air injection device was considered. A modification on conventional injection device (normal air-jacket type) was carried out by changing injection angle from 90  (for conventional) to 45  and 22.5  (for modified). Continuity and one-dimensional momentum balance for the flow field with basic principle of two-phase flow and expressions of slip ratio and friction factor as function of flow rates were formulated. The analytical and experimental investigations were carried out f

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